1. Field
This invention relates in general to corneal reconstruction and in particular to a method and means of regenerating a corneal lamella membrane in an effort to restore vision in patients suffering from failed Laser Corneal Ablation Procedure (LCAP) such as those described as LASIK or LASEK, radial keratomy, keratoconus, corneal abrasions, and trauma. Further, this invention holds promise as a method to devise a integral refractive correcting contact-like lens which can be implanted on top of or into the corneal stroma.
2. Prior Art
Corneal damage is a leading cause of impaired vision and blindness. Scarring due to chemical burns, missile damage, genetic disorders, radial keratomy, or failed LCAP are leading causes of corneal eye damage. In particular, failed LCAP is the most common source of vision loss due to corneal damage. Refractive complications can include too much or too little correction, or an imbalance in correction between the eyes. In some cases, patients who experience improper LCAP may be left near or farsighted or with astigmatism, necessitating spectacles or contact lens wear, or in severe cases, may be faced with blindness. Corneal inflammation is another side effect, which can cause a swelling known as diffuse interface keratitis, leading to corneal hazing, and ultimately, blurred vision. LCAP performed on certain patients with large pupil diameters, thin corneas, or keratoconus, leading to night glare, starbursting, haloes, reduced vision under dim lighting, blurring, or reduced overall visual acuity. At present, only corneal transplants or penetrating keratoplasty, are considered a viable treatment.
Given the enormous media attention given to LCAP, most individuals readily embrace LCAP as a cure-all solution to disposing of their glasses and contact lenses. However, all ophthalmologists readily admit, in their FDA-mandated informed consent that not everyone sees well enough after a LCAP procedure to truly eliminate their use of glasses and contact lenses. In fact, studies have shown that over 2 percent of LCAP patients experience degradation in visual acuity that was uncorrectable through refractive means. Of these patients, debilitating effects due to irregular astigmatism and double vision (due to corneal warping) were common. This is particularly troublesome since, unlike cataract surgery, which restores vision in defective eyes, LCAP is an elective process practiced on healthy eyes. While LCAP is certainly a preferable procedure over radial keratotomy, the success of the procedure and the coupling of medicine and marketing has caused in many patients, who should not have undergone the process to be largely forgotten. Further, intraoperative complications include decentered ablations and flap complications, such as a partial or lost flap.
Postoperative effects due to failed LCAP can include pain as a result of disturbance of the epithelial layer, displacement of the corneal flap, inflammation, or infection. Diffuse interface or lamellar keratitis, also known as ‘DLK’ or Sands of Sahara, is the most serious reaction and can produce corneal hazing, blurred vision, farsightedness, astigmatism, and permanent corneal irregularities. Another equally serious complication is keratoectasia induced by LCAP. Ectasia is the distension of the cornea due to an internal pressure gradient causing the cornea to steepen and distort. The most common side effects of LCAP are dryness of the eyes, night glare, starbursting, haloes, induced spherical aberration, induced coma, and reduced visual acuity. Previous attempts to correct the corneal structure to alleviate the aforementioned conditions have been hampered by the fact that only a fixed quantity of tissue is available for ablative modification. By its' very nature, laser ablation or LCAP removes healthy tissue, thus undermining the structural integrity of the cornea. Replacement tissue is not available due to the fact that no other part of the body has the specialized collagen fibril structure inherent in the cornea.
The most widely practiced means of corneal repair has been the corneal transplant. However, problems of tissue rejection, of immunosuppressive medication, gross refractive errors, and limited supplies of suitable donor tissue hamper transplants. While numerous experiments have been conducted in an effort to create laboratory-grown corneal tissue in vitro, the drawback of most of these methods is that they attempt to generate only one type of corneal cell structure, such as the epithelial or endothelial layers. Stromal creation in the laboratory has in the past been met with limited success since no means have been found that successfully form the delicate collagen fibrils with micron sized diameters and fibril spacing necessary for corneal transparency and diffusive permeability.
Many prior art techniques rely on implanting a polymer of material (other than collagen or collagen that is devoid of fibrils), thus lacking in permeability as well as transparency inherent in native tissue. For example, U.S. Pat. No. 4,505,855 to Bruns and Gross issued Mar. 19, 1985, describes the fabrication of a non-fibrilized collagen button produced by ultracentrifugation for transplantation. This concept suffers from the fact that the lack of a controlled fibril diameter and fibril organizational structure significantly hinders the osmotic pumping of proteins and aqueous media through the fabricated collagen region. The same holds true with gaseous diffusion. As a result, transparency will be impaired. Further, since the collagen button is designed to replace only the damaged corneal stroma, leaving out other vital tissues (the stroma is responsible for 90% of corneal thickness, composed of collagen fibrils and is the principal supportive structure of the cornea. Covering the stroma is the epithelium, a cellular membrane about 5 layers thick, below which is the Bowman's Layer, a thin layer separating epithelium and stroma. On the anterior portion of the stroma is the endothelium layer, responsible for dehydrating the cornea via a sodium-potassium pump mechanism and to maintain corneal optical clarity. Last is the Descemet's membrane, which is the endothelium basement membrane. All these layers are all conspicuously absent in Bruns et al. Also, since the source of collagen is not exclusively from the patient or a sterile genetically engineered source, the possibility of a gross immunologic reaction is significant.
Published U.S. Patent Application No. 88307687 to Werblin and Patel, describes a lens produced from a hydrogel material that is inserted under a corneal cap. As indicated in U.S. Pat. No. 4,505,855 to Bruns et al, dated Mar. 19, 1985, any material that is not identical to native tissue can and will affect optical clarity and diffusive capacity required for a healthy corneal structure.
Again, any means of producing a polymer implant which reduces the diffusion rate of oxygen, lipids, or aqueous media, reduces the effectiveness of the implant. Subtle changes in the intraocular pumping mechanism can cause significant loss in visual acuity. As before, nonnatural polymers can be rejected by the immune system.
Similar implants are revealed in prior art such as that described in European Patent No. 443,094/EP B1 to Kelman & DeVore. They utilize polymerized collagen material in conjunction with a periphery of fibrilized collagen. While providing improvements over simple collagen or other polymer implants, this suffers from the fact that the polymerized collagenous core does not contain fibrils at all as native tissue. Moreover, the fibrils on the periphery are not of the same diameter as in native tissue. As such, the permeability of the implant is low, thus affecting corneal hydration and overall nutritional levels. Further, since the collagen source employed can be derived from nonhuman sources, there is a susceptibility to immunologic effects.
European Patent No. 339,080/EP A1 to Gibson, Lerner, et al., reveals an improved prosthetic corneal implant in that the surface of the polymer is coated with crosslinked or uncrosslinked fibronectin. While this coating does improve epithelial adhesion, the problems of lack of diffusibility, optical clarity, and foreign body rejection are still present.
It is known to inject specialized gels in an effort to improve or change the radius of curvature of the cornea. U.S. Pat. No. 5,681,869 to Villain, et al., describes a biocompatable polyethylene oxide gel for injection into the cornea as a method of tissue augmentation. This procedure suffers from the fact that any gel lacks inherent structural integrity and thus can only augment existing tissue through limited hydrodynamic forces. Optical transmissibility and permeability are limited relative to material produced by the disclosed invention. Foreign body rejection is also possible.
Several prior art references disclose means of corneal repair through application of a suitable topographical ointment or solution. European Patent No. 778,021/EP A1 and Japanese Patent No. 8,133,968 JP to Ohuchi and Kato, disclose a solution of eye drops comprised of water, sodium chloride, potassium chloride, sodium bicarbonate, and taurine. This product suffers from the fact that as essentially a simple buffered isotonic saline solution, it is incapable of rendering any of the structural changes in the cornea required to correct high astigmatism, keratoconus, ectasia, burns, or corneal thinning. Further, the solution of Ohuchi and Kato is capable only of yielding temporary corneal surface relief due to minor, transient optical modifications.
European Patent Publication Nos. WO 00218441 and WO 00240242 to Bowlin & Wnek et al., published Mar. 7, 2002 and April 8th respectively, describe electrospun collagen fibers used a tissue scaffolds. Further, claims are made that the geometry of the electroprocessed matrix can be controlled by microprocessor regulation or by moving the spray nozzle with respect to the conductive target or vice versa. In reality, the electric charge that builds up on an electrospun fiber is significant, and results in whipping effect, which can vary fiber diameter and make precise deposition impossible as the fiber splays about the conductive target. This is because the DC high voltage source used in Bowlin et al., allows a like charge to accumulate on the fiber. As the fiber is ejected, a radius in the fiber will result in like charge repulsive forces to deflect the fiber in the opposite direction, where the radius decreases and the repulsive force increases. This process repeats itself, leading an uncontrolled ability to deposit material at a precise target and pattern. Further, the splaying about of the fibers results in tensile forces which varies the fiber diameter considerably.
The principal goal of the cited invention is to fabricate collagen constructs which serve as cell growth scaffold and to encourage neovascularization or blood vessel in growth. However, cell and vessel in growth are detrimental to a successful corneal collagen fibril structure and if allowed to transpire, would result in blindness. Finally, the precise fibril diameter and mean spacing between such fibrils in that construct necessary for corneal use is not described in Bowlin et al. And the lack of such exact fibril specification, uniform diameter, and matrix pattern would result in reduced optical transparency of the material and insufficient permeability for ocular use.